Time Frame |
From first dose of drug up to 28 days after last dose (up to Month 60)
|
Adverse Event Reporting Description |
All-cause mortality: The total number of deaths occurred during study (from randomization and up to month 60) are reported for all randomized participants, not only for treated participants, and included deaths which occurred after 28 days post last study drug dose. Serious AEs and other AEs: Analysis performed on safety population. The safety population included all participants, regardless of Philadelphia chromosome or transcript status, who received at least 1 dose of study medication.
|
|
Arm/Group Title
|
Bosutinib
|
Imatinib
|
Arm/Group Description |
Participants with Philadelphia chro...
|
Participants with Philadelphia chro...
|
Arm/Group Description |
Participants with Philadelphia chromosome-positive CML received bosutinib tablets at a dose of 400 mg, orally once daily in the core treatment phase of 12 months and continued the same treatment into the extension phase or followed up for safety for up to approximately 4 years, until the end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first.
|
Participants with Philadelphia chromosome-positive CML received imatinib tablets at a dose of 400 mg, orally once daily in the core treatment phase of 12 months and continued the same treatment into the extension phase or followed up for safety for up to approximately 4 years, until the end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first.
|
|
|
Bosutinib
|
Imatinib
|
|
Affected / at Risk (%) |
Affected / at Risk (%) |
Total |
14/268 (5.22%) |
14/268 (5.22%) |
|
|
Bosutinib
|
Imatinib
|
|
Affected / at Risk (%) |
Affected / at Risk (%) |
Total |
98/268 (36.57%) |
68/265 (25.66%) |
Blood and lymphatic system disorders |
|
|
Anaemia |
1/268 (0.37%) |
3/265 (1.13%) |
Thrombocytopenia |
2/268 (0.75%) |
1/265 (0.38%) |
Febrile neutropenia |
0/268 (0.00%) |
2/265 (0.75%) |
Agranulocytosis |
1/268 (0.37%) |
0/265 (0.00%) |
Haemolysis |
0/268 (0.00%) |
1/265 (0.38%) |
Haemolytic anaemia |
0/268 (0.00%) |
1/265 (0.38%) |
Cardiac disorders |
|
|
Myocardial ischaemia |
4/268 (1.49%) |
0/265 (0.00%) |
Atrial fibrillation |
2/268 (0.75%) |
1/265 (0.38%) |
Cardiac failure acute |
2/268 (0.75%) |
0/265 (0.00%) |
Coronary artery disease |
2/268 (0.75%) |
0/265 (0.00%) |
Pericarditis |
2/268 (0.75%) |
0/265 (0.00%) |
Angina pectoris |
1/268 (0.37%) |
0/265 (0.00%) |
Pericardial effusion |
1/268 (0.37%) |
0/265 (0.00%) |
Acute coronary syndrome |
1/268 (0.37%) |
0/265 (0.00%) |
Acute myocardial infarction |
1/268 (0.37%) |
0/265 (0.00%) |
Atrial thrombosis |
1/268 (0.37%) |
0/265 (0.00%) |
Cardiac failure |
1/268 (0.37%) |
0/265 (0.00%) |
Cardiac failure congestive |
1/268 (0.37%) |
0/265 (0.00%) |
Cardio-respiratory arrest |
1/268 (0.37%) |
0/265 (0.00%) |
Coronary artery occlusion |
1/268 (0.37%) |
0/265 (0.00%) |
Pleuropericarditis |
1/268 (0.37%) |
0/265 (0.00%) |
Sinus node dysfunction |
1/268 (0.37%) |
0/265 (0.00%) |
Supraventricular tachycardia |
1/268 (0.37%) |
0/265 (0.00%) |
Congenital, familial and genetic disorders |
|
|
Hydrocele |
1/268 (0.37%) |
0/265 (0.00%) |
Ear and labyrinth disorders |
|
|
Vertigo positional |
1/268 (0.37%) |
0/265 (0.00%) |
Endocrine disorders |
|
|
Thyroid disorder |
0/268 (0.00%) |
1/265 (0.38%) |
Eye disorders |
|
|
Eye haemorrhage |
1/268 (0.37%) |
0/265 (0.00%) |
Ocular hypertension |
1/268 (0.37%) |
0/265 (0.00%) |
Retinal vein occlusion |
1/268 (0.37%) |
0/265 (0.00%) |
Retinopathy |
1/268 (0.37%) |
0/265 (0.00%) |
Gastrointestinal disorders |
|
|
Diarrhoea |
5/268 (1.87%) |
1/265 (0.38%) |
Gastritis |
1/268 (0.37%) |
1/265 (0.38%) |
Pancreatitis acute |
1/268 (0.37%) |
1/265 (0.38%) |
Necrotising oesophagitis |
1/268 (0.37%) |
0/265 (0.00%) |
Abdominal pain |
1/268 (0.37%) |
0/265 (0.00%) |
Abdominal pain upper |
0/268 (0.00%) |
1/265 (0.38%) |
Abdominal wall haematoma |
1/268 (0.37%) |
0/265 (0.00%) |
Anal fissure |
1/268 (0.37%) |
0/265 (0.00%) |
Colitis |
0/268 (0.00%) |
1/265 (0.38%) |
Diverticulum intestinal |
1/268 (0.37%) |
0/265 (0.00%) |
Duodenal ulcer |
1/268 (0.37%) |
0/265 (0.00%) |
Food poisoning |
1/268 (0.37%) |
0/265 (0.00%) |
Gastric ulcer |
0/268 (0.00%) |
1/265 (0.38%) |
Gastrointestinal haemorrhage |
0/268 (0.00%) |
1/265 (0.38%) |
Haemorrhoids |
1/268 (0.37%) |
0/265 (0.00%) |
Hypoaesthesia oral |
0/268 (0.00%) |
1/265 (0.38%) |
Inguinal hernia |
1/268 (0.37%) |
0/265 (0.00%) |
Intra-abdominal haematoma |
0/268 (0.00%) |
1/265 (0.38%) |
Large intestine polyp |
0/268 (0.00%) |
1/265 (0.38%) |
Oedematous pancreatitis |
1/268 (0.37%) |
0/265 (0.00%) |
Pancreatitis |
1/268 (0.37%) |
0/265 (0.00%) |
Rectal haemorrhage |
1/268 (0.37%) |
0/265 (0.00%) |
Small intestinal obstruction |
1/268 (0.37%) |
0/265 (0.00%) |
General disorders |
|
|
Pyrexia |
5/268 (1.87%) |
1/265 (0.38%) |
General physical health deterioration |
0/268 (0.00%) |
1/265 (0.38%) |
Hyperthermia |
0/268 (0.00%) |
1/265 (0.38%) |
Implant site haematoma |
1/268 (0.37%) |
0/265 (0.00%) |
Non-cardiac chest pain |
1/268 (0.37%) |
0/265 (0.00%) |
Swelling face |
0/268 (0.00%) |
1/265 (0.38%) |
Hepatobiliary disorders |
|
|
Cholecystitis acute |
2/268 (0.75%) |
0/265 (0.00%) |
Cholelithiasis |
0/268 (0.00%) |
2/265 (0.75%) |
Hepatitis |
2/268 (0.75%) |
0/265 (0.00%) |
Hepatotoxicity |
2/268 (0.75%) |
0/265 (0.00%) |
Cholecystitis |
1/268 (0.37%) |
0/265 (0.00%) |
Portal vein thrombosis |
0/268 (0.00%) |
1/265 (0.38%) |
Immune system disorders |
|
|
Drug hypersensitivity |
1/268 (0.37%) |
0/265 (0.00%) |
Infections and infestations |
|
|
Pneumonia |
8/268 (2.99%) |
5/265 (1.89%) |
Gastroenteritis |
6/268 (2.24%) |
1/265 (0.38%) |
Cellulitis |
3/268 (1.12%) |
2/265 (0.75%) |
Influenza |
1/268 (0.37%) |
2/265 (0.75%) |
Sepsis |
0/268 (0.00%) |
3/265 (1.13%) |
Urinary tract infection |
1/268 (0.37%) |
2/265 (0.75%) |
Abscess |
1/268 (0.37%) |
1/265 (0.38%) |
Abscess limb |
0/268 (0.00%) |
2/265 (0.75%) |
Appendicitis |
0/268 (0.00%) |
2/265 (0.75%) |
Appendicitis perforated |
0/268 (0.00%) |
1/265 (0.38%) |
Bacteraemia |
1/268 (0.37%) |
0/265 (0.00%) |
Bronchitis |
0/268 (0.00%) |
1/265 (0.38%) |
Candida pneumonia |
1/268 (0.37%) |
0/265 (0.00%) |
Cholecystitis infective |
1/268 (0.37%) |
0/265 (0.00%) |
Fournier's gangrene |
0/268 (0.00%) |
1/265 (0.38%) |
Hepatitis E |
1/268 (0.37%) |
0/265 (0.00%) |
Infected dermal cyst |
0/268 (0.00%) |
1/265 (0.38%) |
Infective pericardial effusion |
1/268 (0.37%) |
0/265 (0.00%) |
Liver abscess |
0/268 (0.00%) |
1/265 (0.38%) |
Lower respiratory tract infection |
1/268 (0.37%) |
0/265 (0.00%) |
Meningococcal sepsis |
0/268 (0.00%) |
1/265 (0.38%) |
Neutropenic infection |
0/268 (0.00%) |
1/265 (0.38%) |
Orchitis |
0/268 (0.00%) |
1/265 (0.38%) |
Oropharyngitis fungal |
1/268 (0.37%) |
0/265 (0.00%) |
Pelvic abscess |
1/268 (0.37%) |
0/265 (0.00%) |
Periorbital cellulitis |
1/268 (0.37%) |
0/265 (0.00%) |
Pyelonephritis |
1/268 (0.37%) |
0/265 (0.00%) |
Respiratory tract infection viral |
0/268 (0.00%) |
1/265 (0.38%) |
Splenic infection |
0/268 (0.00%) |
1/265 (0.38%) |
Upper respiratory tract infection |
1/268 (0.37%) |
0/265 (0.00%) |
Injury, poisoning and procedural complications |
|
|
Fall |
1/268 (0.37%) |
1/265 (0.38%) |
Femoral neck fracture |
2/268 (0.75%) |
0/265 (0.00%) |
Hip fracture |
0/268 (0.00%) |
1/265 (0.38%) |
Patella fracture |
0/268 (0.00%) |
1/265 (0.38%) |
Post procedural haemorrhage |
1/268 (0.37%) |
0/265 (0.00%) |
Road traffic accident |
1/268 (0.37%) |
0/265 (0.00%) |
Subdural haematoma |
1/268 (0.37%) |
0/265 (0.00%) |
Tendon rupture |
1/268 (0.37%) |
0/265 (0.00%) |
Investigations |
|
|
Alanine aminotransferase increased |
6/268 (2.24%) |
0/265 (0.00%) |
Aspartate aminotransferase increased |
2/268 (0.75%) |
0/265 (0.00%) |
Blood creatine phosphokinase increased |
0/268 (0.00%) |
1/265 (0.38%) |
Blood sodium decreased |
0/268 (0.00%) |
1/265 (0.38%) |
Lipase increased |
1/268 (0.37%) |
0/265 (0.00%) |
Transaminases increased |
1/268 (0.37%) |
0/265 (0.00%) |
Metabolism and nutrition disorders |
|
|
Decreased appetite |
1/268 (0.37%) |
0/265 (0.00%) |
Hypomagnesaemia |
1/268 (0.37%) |
0/265 (0.00%) |
Tumour lysis syndrome |
1/268 (0.37%) |
0/265 (0.00%) |
Musculoskeletal and connective tissue disorders |
|
|
Osteoarthritis |
1/268 (0.37%) |
2/265 (0.75%) |
Musculoskeletal chest pain |
2/268 (0.75%) |
0/265 (0.00%) |
Osteochondrosis |
1/268 (0.37%) |
1/265 (0.38%) |
Arthralgia |
1/268 (0.37%) |
0/265 (0.00%) |
Back pain |
0/268 (0.00%) |
1/265 (0.38%) |
Intervertebral disc protrusion |
1/268 (0.37%) |
0/265 (0.00%) |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
|
Rectal cancer |
2/268 (0.75%) |
0/265 (0.00%) |
Chronic myeloid leukaemia |
0/268 (0.00%) |
1/265 (0.38%) |
Bladder papilloma |
0/268 (0.00%) |
1/265 (0.38%) |
Carcinoid tumour of the caecum |
1/268 (0.37%) |
0/265 (0.00%) |
Colon cancer |
1/268 (0.37%) |
0/265 (0.00%) |
Colon cancer metastatic |
1/268 (0.37%) |
0/265 (0.00%) |
Endometrial cancer metastatic |
1/268 (0.37%) |
0/265 (0.00%) |
Fallopian tube cancer stage III |
1/268 (0.37%) |
0/265 (0.00%) |
Fibromatosis |
0/268 (0.00%) |
1/265 (0.38%) |
Hepatocellular carcinoma |
0/268 (0.00%) |
1/265 (0.38%) |
Invasive ductal breast carcinoma |
1/268 (0.37%) |
0/265 (0.00%) |
Lung neoplasm malignant |
1/268 (0.37%) |
0/265 (0.00%) |
Myelodysplastic syndrome |
1/268 (0.37%) |
0/265 (0.00%) |
Prostate cancer |
0/268 (0.00%) |
1/265 (0.38%) |
Prostatic adenoma |
0/268 (0.00%) |
1/265 (0.38%) |
Squamous cell carcinoma |
0/268 (0.00%) |
1/265 (0.38%) |
Transitional cell carcinoma |
1/268 (0.37%) |
0/265 (0.00%) |
Nervous system disorders |
|
|
Haemorrhagic stroke |
1/268 (0.37%) |
1/265 (0.38%) |
Cerebral haemorrhage |
1/268 (0.37%) |
0/265 (0.00%) |
Cerebrovascular accident |
0/268 (0.00%) |
1/265 (0.38%) |
Headache |
1/268 (0.37%) |
0/265 (0.00%) |
Syncope |
0/268 (0.00%) |
1/265 (0.38%) |
Pregnancy, puerperium and perinatal conditions |
|
|
Unintended pregnancy |
2/268 (0.75%) |
0/265 (0.00%) |
Renal and urinary disorders |
|
|
Acute kidney injury |
4/268 (1.49%) |
0/265 (0.00%) |
Chronic kidney disease |
2/268 (0.75%) |
0/265 (0.00%) |
Haematuria |
2/268 (0.75%) |
0/265 (0.00%) |
Renal failure |
1/268 (0.37%) |
0/265 (0.00%) |
Calculus bladder |
0/268 (0.00%) |
1/265 (0.38%) |
Nephrotic syndrome |
0/268 (0.00%) |
1/265 (0.38%) |
Ureterolithiasis |
0/268 (0.00%) |
1/265 (0.38%) |
Urinary incontinence |
0/268 (0.00%) |
1/265 (0.38%) |
Urinary retention |
0/268 (0.00%) |
1/265 (0.38%) |
Reproductive system and breast disorders |
|
|
Ovarian cyst |
0/268 (0.00%) |
1/265 (0.38%) |
Prostatic dysplasia |
0/268 (0.00%) |
1/265 (0.38%) |
Uterine haemorrhage |
1/268 (0.37%) |
0/265 (0.00%) |
Vaginal haemorrhage |
1/268 (0.37%) |
0/265 (0.00%) |
Respiratory, thoracic and mediastinal disorders |
|
|
Pleural effusion |
4/268 (1.49%) |
1/265 (0.38%) |
Dyspnoea |
2/268 (0.75%) |
2/265 (0.75%) |
Chronic obstructive pulmonary disease |
1/268 (0.37%) |
1/265 (0.38%) |
Respiratory failure |
2/268 (0.75%) |
0/265 (0.00%) |
Pneumothorax |
1/268 (0.37%) |
0/265 (0.00%) |
Acute respiratory failure |
0/268 (0.00%) |
1/265 (0.38%) |
Pulmonary hypertension |
1/268 (0.37%) |
0/265 (0.00%) |
Pulmonary oedema |
1/268 (0.37%) |
0/265 (0.00%) |
Pulmonary toxicity |
0/268 (0.00%) |
1/265 (0.38%) |
Respiratory disorder |
1/268 (0.37%) |
0/265 (0.00%) |
Skin and subcutaneous tissue disorders |
|
|
Angioedema |
0/268 (0.00%) |
2/265 (0.75%) |
Dermatitis allergic |
1/268 (0.37%) |
0/265 (0.00%) |
Lichen planus |
0/268 (0.00%) |
1/265 (0.38%) |
Rash |
1/268 (0.37%) |
0/265 (0.00%) |
Rash maculo-papular |
1/268 (0.37%) |
0/265 (0.00%) |
Social circumstances |
|
|
Pregnancy of partner |
2/268 (0.75%) |
1/265 (0.38%) |
Vascular disorders |
|
|
Embolism |
1/268 (0.37%) |
1/265 (0.38%) |
Hypertensive crisis |
2/268 (0.75%) |
0/265 (0.00%) |
Deep vein thrombosis |
1/268 (0.37%) |
0/265 (0.00%) |
Haematoma |
1/268 (0.37%) |
0/265 (0.00%) |
Hypotension |
0/268 (0.00%) |
1/265 (0.38%) |
Hypovolaemic shock |
1/268 (0.37%) |
0/265 (0.00%) |
Term from vocabulary, MedDRA v23.0
Indicates events were collected by non-systematic assessment
|
|
Frequency Threshold for Reporting Other Adverse Events
|
5%
|
|
Bosutinib
|
Imatinib
|
|
Affected / at Risk (%) |
Affected / at Risk (%) |
Total |
264/268 (98.51%) |
260/265 (98.11%) |
Blood and lymphatic system disorders |
|
|
Thrombocytopenia |
96/268 (35.82%) |
53/265 (20.00%) |
Anaemia |
59/268 (22.01%) |
59/265 (22.26%) |
Neutropenia |
33/268 (12.31%) |
61/265 (23.02%) |
Leukopenia |
18/268 (6.72%) |
34/265 (12.83%) |
Lymphopenia |
15/268 (5.60%) |
8/265 (3.02%) |
Eye disorders |
|
|
Periorbital oedema |
4/268 (1.49%) |
44/265 (16.60%) |
Eyelid oedema |
3/268 (1.12%) |
24/265 (9.06%) |
Conjunctival haemorrhage |
2/268 (0.75%) |
18/265 (6.79%) |
Dry eye |
4/268 (1.49%) |
16/265 (6.04%) |
Lacrimation increased |
1/268 (0.37%) |
18/265 (6.79%) |
Vision blurred |
5/268 (1.87%) |
14/265 (5.28%) |
Gastrointestinal disorders |
|
|
Diarrhoea |
201/268 (75.00%) |
106/265 (40.00%) |
Nausea |
100/268 (37.31%) |
112/265 (42.26%) |
Vomiting |
55/268 (20.52%) |
54/265 (20.38%) |
Abdominal pain |
61/268 (22.76%) |
25/265 (9.43%) |
Abdominal pain upper |
28/268 (10.45%) |
26/265 (9.81%) |
Constipation |
36/268 (13.43%) |
17/265 (6.42%) |
Dyspepsia |
26/268 (9.70%) |
24/265 (9.06%) |
Abdominal distension |
14/268 (5.22%) |
8/265 (3.02%) |
Gastrooesophageal reflux disease |
8/268 (2.99%) |
14/265 (5.28%) |
Toothache |
14/268 (5.22%) |
7/265 (2.64%) |
General disorders |
|
|
Fatigue |
57/268 (21.27%) |
54/265 (20.38%) |
Pyrexia |
44/268 (16.42%) |
29/265 (10.94%) |
Oedema peripheral |
20/268 (7.46%) |
43/265 (16.23%) |
Asthenia |
34/268 (12.69%) |
24/265 (9.06%) |
Face oedema |
7/268 (2.61%) |
17/265 (6.42%) |
Influenza like illness |
16/268 (5.97%) |
6/265 (2.26%) |
Infections and infestations |
|
|
Upper respiratory tract infection |
36/268 (13.43%) |
33/265 (12.45%) |
Nasopharyngitis |
36/268 (13.43%) |
30/265 (11.32%) |
Urinary tract infection |
26/268 (9.70%) |
18/265 (6.79%) |
Influenza |
24/268 (8.96%) |
14/265 (5.28%) |
Gastroenteritis |
12/268 (4.48%) |
17/265 (6.42%) |
Bronchitis |
19/268 (7.09%) |
6/265 (2.26%) |
Sinusitis |
15/268 (5.60%) |
8/265 (3.02%) |
Investigations |
|
|
Alanine aminotransferase increased |
90/268 (33.58%) |
16/265 (6.04%) |
Aspartate aminotransferase increased |
69/268 (25.75%) |
18/265 (6.79%) |
Lipase increased |
56/268 (20.90%) |
30/265 (11.32%) |
Blood creatine phosphokinase increased |
14/268 (5.22%) |
33/265 (12.45%) |
Blood creatinine increased |
18/268 (6.72%) |
22/265 (8.30%) |
Amylase increased |
25/268 (9.33%) |
10/265 (3.77%) |
Weight increased |
8/268 (2.99%) |
20/265 (7.55%) |
Blood alkaline phosphatase increased |
17/268 (6.34%) |
7/265 (2.64%) |
Blood bilirubin increased |
17/268 (6.34%) |
7/265 (2.64%) |
Metabolism and nutrition disorders |
|
|
Decreased appetite |
29/268 (10.82%) |
17/265 (6.42%) |
Hypokalaemia |
6/268 (2.24%) |
23/265 (8.68%) |
Hypophosphataemia |
7/268 (2.61%) |
19/265 (7.17%) |
Musculoskeletal and connective tissue disorders |
|
|
Arthralgia |
48/268 (17.91%) |
49/265 (18.49%) |
Muscle spasms |
10/268 (3.73%) |
81/265 (30.57%) |
Pain in extremity |
26/268 (9.70%) |
39/265 (14.72%) |
Myalgia |
13/268 (4.85%) |
48/265 (18.11%) |
Back pain |
32/268 (11.94%) |
25/265 (9.43%) |
Bone pain |
8/268 (2.99%) |
19/265 (7.17%) |
Nervous system disorders |
|
|
Headache |
58/268 (21.64%) |
41/265 (15.47%) |
Dizziness |
25/268 (9.33%) |
23/265 (8.68%) |
Psychiatric disorders |
|
|
Insomnia |
18/268 (6.72%) |
19/265 (7.17%) |
Anxiety |
15/268 (5.60%) |
15/265 (5.66%) |
Depression |
9/268 (3.36%) |
14/265 (5.28%) |
Respiratory, thoracic and mediastinal disorders |
|
|
Cough |
30/268 (11.19%) |
26/265 (9.81%) |
Dyspnoea |
29/268 (10.82%) |
14/265 (5.28%) |
Oropharyngeal pain |
17/268 (6.34%) |
10/265 (3.77%) |
Skin and subcutaneous tissue disorders |
|
|
Rash |
61/268 (22.76%) |
39/265 (14.72%) |
Pruritus |
30/268 (11.19%) |
10/265 (3.77%) |
Dry skin |
20/268 (7.46%) |
14/265 (5.28%) |
Alopecia |
15/268 (5.60%) |
14/265 (5.28%) |
Rash maculo-papular |
13/268 (4.85%) |
16/265 (6.04%) |
Night sweats |
5/268 (1.87%) |
14/265 (5.28%) |
Vascular disorders |
|
|
Hypertension |
26/268 (9.70%) |
29/265 (10.94%) |
Term from vocabulary, MedDRA v23.0
Indicates events were collected by non-systematic assessment
|